Apoptosis: a pivotal event or an epiphenomenon in the pathophysiology of heart failure?

Abstract

EditorialApoptosis: a pivotal event or an epiphenomenon in the pathophysiology of heart failure?Apoptosis, or programmed cell death, is an evolutionary conserved genetically programmed process by which multicellular organisms regulate cell numbers. It is critical in development and in tissue homeostasis. Unlike necrosis, the process is active, energy requiring and precisely regulated. Apoptosis in cardiac development and diseaseCardiac myocytes are by and large terminally diVerentiated and have a limited capacity for self renewal. It would therefore seem that loss of a significant number of cardiomyocytes would have lasting adverse consequences. Apoptosis is, however, integral to normal cardiac development and is also important in the morphogenesis of the conducting system. This can be illustrated by accessory pathway mediated arrhythmias caused by inadequate removal of loop short circuit cells by apoptosis. Apoptotic cardiomyocytes have also been identified in subjects with ischaemic heart disease and myocarditis. Moreover, evidence exists to show that apoptosis occurs in "end stage" heart failure. The relevance of this process in the overall pathophysiology and progression of heart failure is, however, still controversial. We hope to convey the current understanding of apoptosis with respect to its prevalence and its putative impact on chronic stable cardiomyopathy. We will also discuss the theoretical implications of blocking the apoptotic programme in the management of heart failure.Apoptosis and the pathophysiology of heart failure Quantifying the number of apoptotic cells has been fraught with diYculty and the merits of the various analytical techniques for determining apoptosis are vigorously debated.

Hyperglycemia-Induced Apoptosis in Mouse Myocardium

“…Activation of caspase-3 is mediated by multiple pathways, simply divided into mitochondria-dependent and -independent pathways (24,25,30). In the present study, the mitochondria-dependent pathway was examined.…”

“…Caspase-3 plays a pivotal role in the execution of apoptosis (24,30). Cells deficient in caspase-3 were resistant to apoptosis (31).…”

The coordinated increased expression of biliverdin reductase and heme oxygenase‐2 promotes cardiomyocyte survival: a reductase‐based peptide counters β‐adrenergic receptor ligand‐mediated cardiac dysfunction

“…78). In either instance, reduction in apoptosis to basal levels might ultimately be of benefit to patients, although it has been argued that a complete elimination of apoptosis might not be advantageous in the long term (79), as it could result in neoplasia and/or autoimmunity complications.…”

Myocardial Fas and Cytokine Expression in End‐Stage Heart Failure: Impact of LVAD Support

“…Apoptosis, or programmed cell death, is evident in the myocardium of subjects with end‐stage HF who undergo cardiac transplantation, 7,8 and the resultant loss of cardiac myocytes contributes to HF progression 9,10 . The apoptotic program is triggered by the activation of Fas, a transmembrane receptor belonging to the TNF receptor superfamily 11 .…”

“…Studies have shown elevated myocardial TNF‐α, interleukin (IL)‐1β, FasL, and IL‐6 15–19 . Cytokines have been proposed to play an important role in the remodeling of the myocardium and may facilitate apoptosis and HF progression 10,11 . In myocardial cells, the apoptotic signal is transmitted to the IL‐1β‐converting enzyme (ICE) like protease effector cascade by a cytosolic complex of activated Fas with Fas‐associated death domain (FADD) protein and FADD‐like ICE (FLICE) 2 …”